U.S. health officials on Wednesday ordered Pfizer Inc and GlaxoSmithKline PLC to add strong “black box” warnings on their anti-smoking drugs to highlight the risk of serious mental health problems, including suicidal thoughts.

The warnings, which must be added to Pfizer’s Chantix and Glaxo’s Zyban, follow more than five thousand reports of depression, hostility and other behavioral changes, the Food and Drug Administration said.

FDA officials said there was still a need for the medications, their concerns tempered by smoking’s health dangers, such as lung cancer and heart disease.

“We don’t want to scare people off from trying to use the medication to stop smoking. We just want them carefully monitored,” said Dr. Curt Rosebraugh, who oversees the FDA office that reviews smoking-cessation drugs.

Additionally, the FDA strengthened its caution about possible accidents and serious injuries with Chantix linked to loss of consciousness, mental confusion, dizziness and muscle spasms. But it stopped short of adding it to the boxed warning as some health advocates had urged.

Rosebraugh told reporters the FDA could not directly link the reported problems to the drugs, adding that withdrawal from nicotine in tobacco can also cause problems.

The agency is also requiring the companies to conduct additional clinical trials to help determine how serious a problem the mood disorders are, including among patients who already have depression or other similar conditions.

The warnings will limit Pfizer’s ability to run some types of advertisements for Chantix, which the world’s largest drugmaker had been counting on to help revive profits.

THOUSAND OF REPORTS

FDA first alerted patients and doctors about possible mood changes with Chantix in November 2007, and has continued to receive reports of problems.

Overall, the agency received 4,762 reports of serious psychiatric events since Chantix’s 2006 approval. For Zyban and its generic rivals, it received a total 527 reports, it said.

Specifically, the FDA said it received 98 reports of suicide and 188 reports of attempted suicide with Chantix and 14 reports of suicide and 17 attempts with Zyban and related generics.

Chantix, also known as varenicline, is designed to stimulate a type of nicotine receptor in the brain while preventing nicotine from binding to another receptor.

Zyban includes the same active ingredient, bupropion, as Glaxo’s antidepressant Wellbutrin, which already carries a boxed warning about suicide and other behavioral risks.

Both Pfizer and Glaxo said they would add the new warning to their products.

Pfizer said it has already begun studying Chantix in hundreds of schizophrenia patients and was planning another trial that would include people with and without psychiatric disorders.

“The benefits of Chantix outweigh the risks for many patients when used as directed,” said Dr. Briggs Morrison, a Pfizer senior vice president.

But some consumer advocates said the FDA’s Chantix warning was not strong enough for a drug that has been banned for use by pilots.

Thomas Moore, a scientist at the Drug Safety and Policy Institute for Safe Medication Practices, said making the accident caution more prominent was an improvement but it should be as strong as the one for mental side effects.

“Both doctors and patients should carefully weigh the risks and benefits of this drug… and consider alternatives” such as nicotine patches and gums, said Moore, whose group called attention to reported accidents and injuries last year.

By Susan Heavey
WASHINGTON (Reuters)